Drugs useful in the treatment of mental depression and apathy have generally fallen within at least one of three categories: (1) blockers of synaptosomal uptake of norepinephrine; (2) monoamine oxidase inhibitors; and (3) psychomotor stimulants. Serotonin, like norepinephrine, is known to be an important chemical messenger participating in the transmission of nerve impulses in the brain. These messengers are liberated at specific sites on pre-synaptic cells and received, to complete transmission of the impulse, at specific sites on post-synaptic cells. Their effect is then terminated by metabolism or by uptake into the pre-synaptic cells. Recently, the antidepressant activity of two new drugs, zimelidine and fluvoxamine, has been attributed to their ability to selectively block the uptake of serotonin (compared to norepinephrine blockade). It is thus becoming a widely held view in the medicinal chemistry field that drugs capable of blocking the pre-synaptosomal uptake of serotonin in the brain, thereby alleviating serotonin abnormalities at adjacent post-synaptic receptor sites, will comprise an additional major category of antidepressant agents.
U.S. Pat. Nos. 4,029,731 and 4,045,488 disclose a series of 4-phenyl-1,2,3,4-tetrahydro-naphthalen-1-amines and substituted amines useful as antidepressant agents. The trans-isomeric forms of these prior art compounds possess much greater antidepressant activity than the corresponding cis-isomeric forms. The preferred embodiment, the enantiomer trans-(1R)-N-methyl-4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine and its pharmaceutically acceptable acid addition salts, exhibits excellent synaptosomal norepinephrine uptake blocking activity.